Ophthalmology Month in Review: July 2023

For our July 2023 ophthalmology month in review, the HCPLive editorial team compiled our live, on-site interview content from the American Society of Retina Specialists (ASRS) 41st Annual Scientific Meeting.

We spoke with more than a dozen experts on their respective presentations: new data on approved treatments for geographic atrophy, upcoming agents in the pipeline for retinal diseases, and updates on the port delivery system (PDS) with ranibizumab.

In other news, the FDA approved the first-and-only treatment for Demodex Blepharitis and an artifical intelligence chatbot improved over time on an ophthalmic knowledge assessment.

ASRS 2023

Sophie J. Bakri, MD: The Substantial Burden of Geographic Atrophy

Results from the MOSAIC study showed the substantial burden of geographic atrophy (GA) on both patients with the debilitating disease and their caregivers across the United States and Canada.

From a survey of more than 140 patients with GA and nearly 150 unpaid caregivers, patients reported the inability to drive, a need for help in their daily lives, and a change in their living situation due to GA, while caregivers reported burden and time missed from work.

“In addition, there’s an impact on mental health, frustration, worry about vision, and inability to control their finances,” investigator Sophie J. Bakri, MD, chair and professor of ophthalmology at Mayo Clinic, told HCPLive on the impact of GA on patients. “Just a general sort of lack of control over their life.”

Paul Hahn, MD: A Cross-Trial Comparison of Pegcetacoplan and Avacincaptad Pegol

A cross-trial comparison of the phase 3 OAKS and DERBY studies and the GATHER trial program revealed a greater reduction in GA lesion growth with monthly pegcetacoplan compared to avacincaptad pegol at month 12.

“The best thing to do would be a head-to-head clinical trial comparing 1 drug versus another, but it is very difficult to do and most likely won’t be done,” Hahn said. “Instead, there is the cross-trial anchored matching-adjusted indirect comparison approach, a well-validated approach used in ophthalmology and other fields. It tries to match the inclusion and exclusion criteria between 2 different trials and then balances those matched populations to have a similar group between 2 different trials and then you can compare the results.”

The trial comparison data showed the pooled effect for pegcetacoplan versus avacincaptad pegol was –0.589 mm2 (P <.05), a 30.4% statistically significant greater reduction in change in GA lesion growth with pegcetacoplan.

Arshad Khanani, MD: 48-Week Results of BEHOLD Study on UBX1325 for DME

The BEHOLD study indicates the safety, tolerability, and efficacy of UBX1325 in patients with diabetic macular edema (DME), who have residual visual acuity deficits and macular edema after ≥6 months of anti-vascular endothelial growth factor (VEGF) therapy.

At 48 weeks, data showed a gain of 6.2 letters, maintenance of anatomy, and no cases of intraocular inflammation, retinal vasculitis, or retinal artery occlusion in patients treated with UBX1325

“The next study, the ASPIRE study, will be looking at patients with UBX1325 compared to a standard of care control arm,” Khanani said. “And obviously, we are looking forward to participating in that trial because it’s a novel mechanism of action. And we need to look into it further because of the positive data we have seen from the BEHOLD study.”

David Lally, MD: Efficacy of Oral APX3330 for Diabetic Retinopathy

The phase 2 Zeta-1 trial missed its primary endpoint, as only 8% of eyes treated with oral APX3330 showed ≥2-step diabetic retinopathy severity scale (DRSS) improvement. However, the oral, novel, small molecule inhibitor of Ref-1 did prevent ≥3-step worsening in binocular DRSS compared to placebo, suggesting the need for further clinical development.

“In phase 2 trials, we are often learning about the drug’s potential efficacy for the first time, as is the case with this trial and this novel mechanism of action,” Lally said. “And, sometimes other efficacy signals seen can redirect development plans into phase 3.”

Dennis M. Marcus, MD: Phase 3 Updates on the Port Delivery System

Additional findings from the phase 3 Pagoda and Pavilion trials suggest a benefit of the port delivery system (PDS) with ranibizumab for patients with DME and diabetic retinopathy, offering the potential for functional and anatomic improvements without the need for frequent anti-VEGF injections.

Approved by the FDA in 2021, the PDS was recalled in October 2022 by Genentech/Roche after laboratory testing revealed suboptimal implant performance. Since the recall, Marcus noted there has been testing of improvements in the manufacturing processes, particularly regarding the potential for septum dislodgement, as well as changes made to optimize the performance of the implant.

“The anticipation is to be able to implant patients in clinical trials and then testing by the end of 2023,” Marcus said. “With the goal of engaging the FDA with also reimplanting patients with the hope of bringing the commercial product (Susvimo) back to patients and doctors for further options. So far, the testing indicates that the manufacturing has improved both the implant and the refill needles.”

Aleksandra Rachitskaya, MD: Time to Retinal Fluid Control With Faricimab in DME

Faricimab was associated with reduced time to retina fluid control, with fewer injections versus aflibercept, in patients with DME, according to a posthoc analysis of the phase 3 YOSEMITE/RHINE studies.

More patients achieved an absence of intraretinal fluid with faricimab versus aflibercept through year 2 of the study, at more than 8 months faster. The time to the 50th percentile for the first absence of IRF was 84 weeks for the aflibercept Q8W arm after a median of 12 injections, compared with 48 weeks for the faricimab Q8W and treat-and-extend arms.

“I think looking at the data like that, it shows that potentially early treatment with faricimab to stabilize retinal vessels might lead to better outcomes that are beyond just treatment with anti-VEGF agents,” Rachitskaya said.

In Other News

FDA Approves Lotilaner Ophthalmic Solution for Treatment of Demodex Blepharitis

The FDA approved lotilaner ophthalmology solution 0.25% (XDEMVY™), formerly known as TP-03, for the treatment of Demodex blepharitis. Announced by Tarsus Pharmaceuticals Inc., the ophthalmic solution is the first-and-only FDA-approved treatment to directly target Demodex mites, the root cause of the common eyelid disease.

“Demodex blepharitis, easily diagnosed by the presence of eyelash collarettes, can result in ocular damage in multiple ways, including irritation, eyelash distention or loss, and inflammation, which can be uncomfortable for patients,” Christopher Starr, MD, associate professor of ophthalmology and director of refractive surgery, ophthalmic education, and the cornea fellowship program at Weill Cornell Medicine, New York Presbyterian Hospital, said in a statement. This new medicine is a positive step forward for the treatment of this disease in many patients who have been struggling for years.”

Artificial Intelligence Chatbot Appears to Improve on Ophthalmic Knowledge Assessment

An updated version of the AI chatbot, ChatGPT-4, showed correct responses to 84% of multiple-choice practice questions on a common practice resource to prepare for ophthalmology board certification.

The study expanded previous findings showing the previous version of the chatbot correctly answered 46% of the multiple-choice questions in January 2023 and 58% in February 2023.

“Performance of the updated version of this chatbot across all question categories on OphthoQuestions appeared to improve compared with the performance of the previous version,” wrote the investigative team, led by Rajeev H. Muni, MD, MSc, from the department of ophthalmology and vision sciences at the University of Toronto. “Results of this study also suggest that in most cases, the updated version of the chatbot generated accurate responses when options were given.”